Experimental Urethral Infection with Neisseria gonorrhoeae

Waltmann, Andreea; Duncan, Joseph A.; Pier, Gerald B.; Cywes‐Bentley, Colette; Cohen, Myron S.; Hobbs, Marcia M.

doi:10.1007/82_2021_250

Cited by 10 publications

(9 citation statements)

References 77 publications

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“…gonorrhoeae vaccine development was an active area of research 4-5 decades ago, but disappointing clinical trial results detailed below, a heightening of the HIV epidemic, and availability of effective antibiotic therapies for treatment of infection dampened enthusiasm for further efforts for a substantial period. Five trials tested the efficacy of three different vaccine preparations in the field, with the N. gonorrhoeae controlled human infection model (CHIM), or by a combination of these methods (Table 1), reviewed most recently in [3,4]. Though no field trial of the vaccines succeeded in demonstrating protection against naturally acquired infection, important vaccine-induced protection lessons were gained.…”

Section: Past N Gonorrhoeae Vaccine Trialsmentioning

confidence: 99%

Promising developments in gonococcal vaccines

Waltmann,

Chen,

Duncan

2023

Current Opinion in Infectious Diseases

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Purpose of review While effective vaccines to prevent invasive infections by Neisseria meningitidis have been deployed around the world, development of a vaccine to prevent Neisseria gonorrhoeae has lagged. After multiple failed vaccine candidates, vaccine development for N. gonorrhoeae is showing promise for the first time in several decades. This review highlights recent progress in the field. Recent findings Vaccines containing outer-membrane vesicles (OMV) have been used to manage outbreaks of the serogroup B N. meningitidis in a number of countries. Epidemiologic studies indicate these vaccination campaigns were associated with reductions in reported N. gonorrhoeae infections. Recently, a serogroup B N. meningitidis vaccine containing both recombinant antigens and OMV has been licensed through much of the world. Epidemiologic studies also demonstrate associations between 4CMenB immunization and reduced N. gonorrhoeae infections. Additionally, mathematical modeling studies have begun to identify potential strategies for vaccine deployment to maximize reduction of infections. Summary After several decades with little progress towards an effective gonococcal vaccine, large observational studies have provided evidence that a new generation of group B N. meningitidis vaccines containing OMV have serendipitously restarted the field. Ongoing clinical trials will soon provide definitive evidence regarding the efficacy of these vaccines in preventing N. gonorrhoeae infection.

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Section: Past N Gonorrhoeae Vaccine Trialsmentioning

confidence: 99%

Promising developments in gonococcal vaccines

Waltmann,

Chen,

Duncan

2023

Current Opinion in Infectious Diseases

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“…It is the most relevant model of natural gonococcal infection that is available today, but only for men; women cannot be infected with gonococci because of the possibility of infection ascending into the upper reproductive tract and causing pelvic inflammatory disease (PID) and other complications. The Ng CHIM was developed during the 1980s by researchers at the Walter Reed Army Institute of Research and at the University of North Carolina, Chapel Hill, and is reviewed extensively by Waltmann et al [ 26 ]. A step-by-step experimental protocol is available [ 27 ], and has been used for both vaccine and pathogenesis studies.…”

Section: Vertebrate Animal Modelsmentioning

confidence: 99%

“…The findings from this study with the Ng CHIM were that immunity against PorB, LOS and Opa ‘transpired theoretically to predict protection from infection’, whereas Rmp was subversive for PorB immunogenicity in humans and enhanced the likelihood of infection [ 31 , 32 ]. In contrast to active immunization, there is one recent report of a passive protection study using the Ng CHIM to test the hypothesis that a human monoclonal antibody raised to β-(1-6)-linked poly-N-acetyl-d-glucosamine (PNAG), and bactericidal for gonococci, could prevent gonococcal infection [ 26 ]. Infusion of this monoclonal antibody did not reduce bacterial load in the urine of infected volunteers, with four out of seven infused volunteers, and one out of three control volunteers, i.e., without antibody infusion, developing urethritis.…”

Section: Vertebrate Animal Modelsmentioning

confidence: 99%

Vertebrate and Invertebrate Animal and New In Vitro Models for Studying Neisseria Biology

Girgis

Christodoulides

2023

Pathogens

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The history of Neisseria research has involved the use of a wide variety of vertebrate and invertebrate animal models, from insects to humans. In this review, we itemise these models and describe how they have made significant contributions to understanding the pathophysiology of Neisseria infections and to the development and testing of vaccines and antimicrobials. We also look ahead, briefly, to their potential replacement by complex in vitro cellular models.

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“…Rectal and pharyngeal infections are usually asymptomatic in both men and women (Dombrowski, 2021 ). Experimental infection of women with N. gonorrhoeae is unsafe due to the potential for ascension of bacteria into the upper urogenital tract, whereas a controlled human male urethral infection model that replicates the natural course of the disease has been safely used over the last 3 decades to study pathogenicity and immunity in several hundred subjects who were inoculated with strains FA1090 and MS11 (Cohen et al, 1994 ; Hobbs and Duncan, 2019 ; Waltmann et al, 2022 ). These strains have also been used to examine murine antisera reactivity to the 4CMenB meningococcal recombinant protein-detoxified outer membrane vesicle vaccine (Leduc et al, 2020 ) and preclinical testing of an LOS peptide mimetic vaccine (Gulati et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Comparison of lipooligosaccharides from human challenge strains of Neisseria gonorrhoeae

John,

Phillips,

Cardenas

et al. 2023

Front. Microbiol.

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The alarming rise of antibiotic resistance and the emergence of new vaccine technologies have increased the focus on vaccination to control gonorrhea. Neisseria gonorrhoeae strains FA1090 and MS11 have been used in challenge studies in human males. We used negative-ion MALDI-TOF MS to profile intact lipooligosaccharide (LOS) from strains MS11mkA, MS11mkC, FA1090 A23a, and FA1090 1-81-S2. The MS11mkC and 1-81-S2 variants were isolated from male volunteers infected with MS11mkA and A23a, respectively. LOS profiles were obtained after purification using the classical phenol water extraction method and by microwave-enhanced enzymatic digestion, which is more amenable for small-scale work. Despite detecting some differences in the LOS profiles, the same major species were observed, indicating that microwave-enhanced enzymatic digestion is appropriate for MS studies. The compositions determined for MS11mkA and mkC LOS were consistent with previous reports. FA1090 is strongly recognized by mAb 2C7, an antibody-binding LOS with both α- and β-chains if the latter is a lactosyl group. The spectra of the A23a and 1-81-S2 FA1090 LOS were similar to each other and consistent with the expression of α-chain lacto-N-neotetraose and β-chain lactosyl moieties that can both be acceptor sites for sialic acid substitution. 1-81-S2 LOS was analyzed after culture with and without media supplemented with cytidine-5'-monophosphate N-acetylneuraminic acid (CMP-Neu5Ac), which N. gonorrhoeae needs to sialylate its LOS. LOS sialylation reduces the infectivity of gonococci in men, although it induces serum resistance in serum-sensitive strains and reduces killing by neutrophils and antimicrobial peptides. The infectivity of FA1090 in men is much lower than that of MS11mkC, but the reason for this difference is unclear. Interestingly, some peaks in the spectra of 1-81-S2 LOS after bacterial culture with CMP-Neu5Ac were consistent with disialylation of the LOS, which could be relevant to the reduced infectivity of FA1090 in men and could have implications regarding the phase variation of the LOS and the natural history of infection.

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Experimental Urethral Infection with Neisseria gonorrhoeae

Cited by 10 publications

References 77 publications

Promising developments in gonococcal vaccines

Promising developments in gonococcal vaccines

Vertebrate and Invertebrate Animal and New In Vitro Models for Studying Neisseria Biology

Comparison of lipooligosaccharides from human challenge strains of Neisseria gonorrhoeae

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